Project Summary: We have devised small, metallic, wireless microdevices, called microgrippers (-grippers). The - grippers are approximately 1 mm in size and have finger-like projections. The -grippers can be delivered within the gastrointestinal (GI) tract via a catheter inserted through the endoscope. Preliminary data shows that, in animal models in vivo, -grippers can be delivered, spread uniformly to the mucosa, can be closed and biopsy tissue in response to biologic cues (such as temperature), can be retrieved, and that the biologic material collected can be analyzed cytologically and molecularly (RNA and DNA). The overarching hypothesis of the current proposal is that efficient statistical sampling of biologic tissue will dramatically improve disease diagnostic ability. We will perform animal studies in the esophagus and will gear towards application of this technology for human esophageal disorders, such as Barrett's esophagus. We plan to 1) refine engineering aspects of the -grippers; 2) refine endoscopic tools for -gripper retrieval; 3) characterize the sensitivity and specificity of -grippers; 4) refine molecular biology analyses to be implemented using biologic material retrieved by the -grippers and finally, 5) perform all required animal studies under FDA guidance in preparation for a Phase I Clinical Trial in humans. The motivation for these studies comes from the fact that biologic tissue, obtained via biopsy, represents the diagnostic cornerstone for a variety of human medical conditions, including cancer. In brief, current biopsying protocols are of 2 major types: 1. Biopsying of a lesion that is visualized and perceived to represent pathologic tissue; and 2. Biopsying tissue randomly, since no lesion is visible. In the first case, the current biopsy forceps, and its variations, is an appropriate tool. In the second case, however, it is not. A plethora of human conditions require random biopsies (such as Ulcerative Colitis, Barrett's esophagus, etc). The relative large size of the biopsy forceps, coupled with its serial maneuvering severely limit the number of biopsies that can be performed, and by extension, the mucosal coverage. What we propose is a paradigm shift: instead of using large, tethered biopsy forcepses, we will implement miniature, tether-free tools that can perform biopsying at tens to hundreds to thousands of locations simultaneously. Although preliminary data demonstrates that we can perform cytologic examinations on the biologic tissue retrieved, we plan on concentrating on molecular markers. Recent years brought phenomenal genetic and epigenetic information regarding human disease, in particular cancers. Our work will bring us closer to implementing these markers to human disease. We envision that the statistical sampling performed with the - grippers, coupled with biologic analyses of various RNA and DNA markers (mRNA, microRNA, methylation, mutations, etc) will revolutionize diagnostics in medicine.